Previous studies have proposed that insulin increases the binding of insulin-like growth factor II (IGF-II) in isolated rat adipose cells by increasing receptor affinity (Ka). This study re-examines these observations under conditions in which receptor-ligand internalization is blocked by 1 mM KCN. The results suggest that (a) the effects of KCN reflect a selective blockade of endocytosis; (b) in the absence of KCN, IGF-II binds to receptors of constant affinity that cycle between the plasma membrane and an intracellular pool resulting in an accumulation of intracellular IGF-II; (c) insulin induces an increase in IGF-II binding by causing a steady state redistribution of receptors from this intracellular pool to the plasma membrane; and (d) this redistribution in the intact cell can only be detected using Scatchard analysis when recycling of the receptors is prevented by KCN. A comparison of insulin's effects on glucose transport and cell surface IGF-II receptors has also been undertaken in rat adipose cells using 3-0-methylglucose transport as a measure of glucose transport activity and Scatchard analysis of IGF-II binding in the presence of KCN to determine cell surface IGF-II receptor number. These results demonstrate that while the characteristics of the stimulatory action of insulin on glucose transport activity and cell surface IGF-II receptor number are qualitatively similar, quantitative differences are clearly demonstrable which suggest that the subcellular cycling of these two integral membrane proteins occurs by distinct processes.